1. Surgical Animal Models for Studying Cardiac Hypertrophy and Failure The Director of the Animal Physiology Core has developed a number of surgical models that induce cardiac hypertrophy and failure in the rodent. In Projects 1,2 and 3 (Solaro, Russell, Lewandowski), transverse thoracic aortic banding will be used to examine the effect of superimposing a systolic pressure overload on mice that overexpress transgenes of sarcomeric and intracellular signaling proteins in the heart. Project 2 also includes a model of arteriovenous insufficiency in mice to induce a volume overload on the left ventricle. Guinea pigs (DeTombe, Project 4) will be subjected to pressure and volume overload induced by transverse thoracic aortic coarctation or aortic insufficiency (aortic valve leaflet damage). These studies will examine the effect of ventricular remodeling and failure on isolated muscle function and the role that phosphorylation of sarcomeric proteins play in cardiac dysfunction.